Cesium carbonate → 2-(2-(1,3-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-N-methylbenzamide

HRID 1045952Notes

Reaction equation

HRID 1045952 reaction equation
Cl[C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[C:10]=2[C:11]([NH:13][CH3:14])=[O:12])[C:5]([C:21]([F:24])([F:23])[F:22])=[CH:4][N:3]=1.[CH3:25][N:26]1[C:30]([NH2:31])=[CH:29][C:28]([CH3:32])=[N:27]1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:25][N:26]1[C:30]([NH:31][C:2]2[CH:7]=[C:6]([NH:8][C:9]3[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[C:10]=3[C:11]([NH:13][CH3:14])=[O:12])[C:5]([C:21]([F:24])([F:23])[F:22])=[CH:4][N:3]=2)=[CH:29][C:28]([CH3:32])=[N:27]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 5207211,3-Dimethyl-1H-pyrazol-5-amineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 866551442-(2-Chloro-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-N-methylbenzamide

Product 1

HCID 569512912-(2-(1,3-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-N-methylbenzamideYield 44%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

2-(2-Chloro-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-N-methylbenzamide (1.66 g, 4.61 mmol), 1,3-dimethylpyrazol-5-amine (0.523 g, 4.71 mmol), palladium(II) acetate (0.083 g, 0.37 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.427 g, 0.74 mmol) and cesium carbonate (1.804 g, 5.54 mmol) were mixed together in dioxane (30 mL). The reaction was degassed with argon and was stirred at 90° C. for 3 hours under argon. The mixture was filtered, the filtrate concentrated and purified twice by flash chromatography on silica gel eluting with 0 to 4% MeOH in DCM/EtOAc (60:40). The solvent was evaporated to dryness to afford 2-(2-(1,3-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-N-methylbenzamide (0.882 g, 44.0%) as a beige solid. 150 mg of this material was dissolved in acetonitrile, concentrated and diluted with DCM. Crystals appeared slowly. The resulting crystalline solid was collected by filtration, washed with DCM and dried to a constant weight to afford 2-[[2-[(2,5-dimethylpyrazol-3-yl)amino]-5-(trifluoromethyl)-4-pyridyl]amino]-6-methoxy-N-methyl-benzamide (110 mg, 32.3%) as a white crystalline solid. Melting onset of 163° C.

Workup

  1. customThe reaction was degassed with argon
  2. filtrationThe mixture was filtered
  3. concentrationthe filtrate concentrated
  4. custompurified twice by flash chromatography on silica gel eluting with 0 to 4% MeOH in DCM/EtOAc (60:40)
  5. customThe solvent was evaporated to dryness

Sources & evidence

ORD record
ord-a6524fc6b5e7499fadefadb0f404237d
Source dataset
uspto-grants-2013_10
Patent number
US08569298B2

Reaction notes

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